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Title: Presynaptic control of corticostriatal inputs : role of GABA
Author: Logie, Christopher
ISNI:       0000 0004 5364 116X
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2014
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The basal ganglia (BG) are a group of nuclei in the basal forebrain critical in movement, goal directed behaviour and action selection. Cortical projections to the largest BG nucleus, the striatum, are highly important in theories of BG function. Therefore, we have investigated the role of striatal neurons in modulating the activity of corticostriatal synapses. In an in-vitro preparation of rodent brain slices, we conducted whole-cell patch clamp recordings of single and pairs of striatal neurons and recorded responses of medium spiny neurons (MSNs) to stimulation of corticostriatal fibres. In the presence of opioid, GABAA, NK1 and cholinergic receptor antagonists, antidromic stimulation of a population of MSNs (5 stims, 50 Hz) caused suppression of subsequently evoked EPSPs in MSNs. This suppression was dependent upon the interval between antidromic MSN stimulation and the stimulation of evoked EPSPs; suppression was larger at 500 ms intervals than at 1 or 2 s intervals. These effects were completely blocked by the GABAB antagonist CGP 52432. Bursts of evoked action potentials (5 APs, 50 Hz) in a single MSN were insufficient to cause these effects in a nearby MSN. Similar spikes in single fast spiking interneurons and low threshold spiking interneurons (LTSIs) were also insufficient. Conversely, single neurogliaform interneurons (NGFIs) could suppress evoked EPSPs in nearby MSNs in a GABAB-dependent manner. This suppression was more likely in NGFI-MSN pairs that exhibited direct GABAergic interactions. We also tested long depolarisations in LTSIs, a protocol that preferentially releases NO, which was shown to suppress evoked EPSPs through a non-GABAergic mechanism. Finally, we tested the application of exogenous NPY to slices, which also inhibited corticostriatal transmission. These results provide the first demonstration of how GABAB receptors at corticostriatal synapses are activated by endogenous GABA released by striatal neurons. They also reveal novel mechanisms through which striatal factors influence these synapses.
Supervisor: Turner, Jonathan; Turner, Jonathan Sponsor: BBSRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: striatum ; electrophysiology ; GABA ; corticostriatal ; action selection